B-type natriuretic peptide, vascular endothelial growth factor, endothelin-1, and nitric oxide synthase in chronic mountain sickness

The pathogenesis of chronic mountain sickness (CMS) may involve vasoactive peptides. The aim of this study was to investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). A total of 24 patients with CMS and 50 control subjects residing at 4,300 m participated in this study. Mean pulmonary arterial pressure (mPAP) was measured by echocardiography. Serum BNP, VEGF, ET-1, and eNOS were measured. Receiver operator characteristic curves to assess the balance of sensitivity and specificity for CMS were constructed. As a result, patients with CMS had significantly greater mPAP compared with controls and had lower arterial O2 saturation (SaO2). Both BNP and ET-1 correlated positively with mPAP and negatively with Sa _O2, whereas serum VEGF levels were inversely correlated with Sa _O2; eNOS correlated negatively with mPAP and positively with Sa _O2. Median concentrations of BNP were greater in patients with CMS compared with those without CMS: 369 pg/ml [interquartile range (IQR) {box drawings double horizontal} 336-431] vs. 243 pg/ml (IQR {box drawings double horizontal} 216-279); P < 0.001. Similarly, concentrations of VEGF [543 pg/ml (IQR {box drawings double horizontal} 446-546) vs. 243 pg/ml (IQR {box drawings double horizontal} 216-279); P < 0.001] and ET-1 [14.7 pg/ml (IQR {box drawings double horizontal} 12.5-17.9) vs. 11.1 pg/ml (IQR {box drawings double horizontal} 8.7- 13.9); P {box drawings double horizontal} 0.05] were higher in those with CMS compared with those without, whereas eNOS levels were lower in those with CMS [8.90 pg/ml (IQR 7.59 -10.8) vs. 11.2 pg/ml (9.13-13.1); P < 0.001]. The areas under the receiver operator characteristic curves for diagnosis of CMS were 0.91, 0.93, 0.77, and 0.74 for BNP, VEGF, ET-1, and eNOS, respectively. In age- and biomarker-adjusted logistic regression, BNP and VEGF were positively predictive of CMS, whereas eNOS was inversely predictive. In conclusion, severe chronic hypoxemia and consequent pulmonary hypertension in patients with CMS may stimulate release of natriuretic peptides and angiogenic cytokines. These vasoactive peptides may play an important role in the pathogenesis and clinical expression of CMS and may indicate potential prognostic factors in CMS that could serve as targets for therapeutic trials or clinical decision making.